Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of ovariectomy and hormone replacement in control and carcinogen treated female rats were investigated by measuring whole blood and liver glutathione (WGSH, HGSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GRx) and histological evaluation. Hepatocarcinogenesis was induced by diethylnitrosamine and 2-acetylaminofluorene. In control rats not receiving carcinogen, ovariectomy significantly increased the GST and GRx activities. Replacement with either estrogen or progesterone reduced the GST activities to below intact female values whereas replacement of both hormones together brought the GST activities to that of intact females. GRx activities were brought to intact female values by replacement with estrogen or progesterone, either singly or in combination. Neither ovariectomy nor sex hormone/s replacement influenced the levels of WGSH, HGSH and GPx activities. Carcinogen administration to intact rats increased all the parameters measured. Ovariectomized rats treated with carcinogen showed lower GPx and GRx activities at 2 mths. However, replacement with either progesterone or combined estrogen and progesterone increased GPx and GRx activities to original values. On the other hand GST and GPx activities in ovariectomized rats which had carcinogen treatment were lower than intact rats after 5 mths. Replacement with hormones either singly or both brought GST and GPx activities up to intact rat levels receiving carcinogen. The levels of WGSH, HGSH and GRx activities (5 mths) in carcinogen treated rats were not influenced by ovariectomy and/or hormone/s replacement. The results from this study suggested that ovariectomy reduced the severity of hepatocarcinogenesis which was restored by sex hormone/s replacement.
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PMID:Effect of ovariectomy and sex hormone replacement on glutathione and glutathione-related enzymes in rat hepatocarcinogenesis. 760 48

Hepatocarcinogenesis was examined in an initiation--promotion protocol with a single initiating dose of 7,12-dimethylbenz[a]anthracene (DMBA) followed by promotion with phenobarbital (PB) in the Nagase analbuminemic rat (NA), the Sprague-Dawley rat (SD) and their F1 crosses. All rats received a 70% partial hepatectomy, followed at 24 h by 30 mg DMBA/kg body wt or the solvent. After a 2 week recovery following surgery, half of the solvent control and initiated groups received either basal diet or promotion with 0.05% PB mixed into the basal NIH-07 diet. After 12 weeks of promotion, the rats were killed and the livers perfused and fixed in situ with paraformaldehyde. Liver slices were paraffin embedded and stained for the placental isozyme of glutathione S-transferase (PGST). The number of altered hepatic foci (AHF) expressing PGST per liver was determined by quantitative stereology and used as an endpoint for comparison of initiation in the rat strains. The NA rat had a lower response to this initiation-promotion protocol than did the SD rat. The F1 progeny of the male NA and female SD rats were more similar to the NA parent in their responsiveness to initiation, whereas the F1 progeny of the female NA and male SD were similar to the SD parent in this respect. Putative mutagenesis and carcinogenesis were examined in the F1 progeny of the female NA and male SD rat. In these rats, serial liver sections were stained either for albumin to detect putative mutations at that locus, or PGST to identify putatively initiated hepatocytes. In the NA/SD F1, the number of single hepatocytes with a putative mutation at the albumin locus was the same (3.7 x 10(5)/liver) as those expressing a common marker of preneoplasia (PGST). The number of AHF expressing PGST was approximately 5% that of the single cells exhibiting an altered expression of albumin or PGST, indicating a possible quantitative correlation between initiation and mutation in vivo when individual hepatocytes with altered gene expression were counted. These studies also suggest that only a subpopulation of the putatively initiated hepatocytes expands clonally in the presence of the promoting agent, PB. The progeny of the female NA rat crossed with the SD male rat appears to provide a useful model in which to compare mutation and carcinogenesis simultaneously in vivo.
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PMID:Comparison of hepatocyte phenotypes at the glutathione transferase and albumin loci in Sprague-Dawley and Nagase analbuminemic rats and F1 progeny after initiation and promotion. 833 Mar 43

Epidemiological studies show an increased risk of developing liver cancer among alcoholics. There is some agreement that ethanol itself is not carcinogenic, but it may enhance the tumorigenic process by inducing drug-metabolizing enzymes, suppression of the immune system or by affecting DNA repair enzymes. Precisely how ethanol predisposes or promotes the development of hepatoma is unknown. Hepatocarcinogenesis induced by a choline-deficient, ethionine-supplemented (CDE) diet produces extensive alteration of the liver architecture with the emergence and rapid proliferation of oval cells. This study examines whether chronic alcohol consumption induces the proliferation of oval cells. Oval cells induced in rats maintained on a 5% ethanol liquid diet (ELD) for up to 24 months, or fed a CDE diet for up to 4 weeks, are compared using a panel of liver-specific markers. In CDE-treated rats, oval cells staining positively for alpha-fetoprotein (AFP), pi-class glutathione S-transferase (pi GST), and the embryonic form of pyruvate kinase (M2-PK) are observed after 1 week. Similar cells are seen in ELD-treated rats after 2 months. Their numbers increase with time, and incorporation of [3H]thymidine confirms they are a dividing population. Acute damage induced by partial hepatectomy and CCI4 poisoning did not induce the appearance of oval cells. We conclude that chronic ethanol consumption induces oval cell proliferation. We suggest that, in addition to other proposed mechanisms, an alteration in cellular composition of the liver be considered as an explanation for the increased incidence of liver cancer among alcoholics.
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PMID:Appearance of oval cells in the liver of rats after long-term exposure to ethanol. 855 34

1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented continuously for 8 weeks in the diets of normal rats and rats chemically induced with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as well as placental glutathione S-transferase (PGST) and GGT activities histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The supplementation was started at three different times: simultaneously with DEN administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of plasma GGT activities and formation of PGST and GGT positive foci were attenuated significantly (P < 0.05) when alpha-T and gamma-T were supplemented simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after cancer induction did not affect plasma enzyme activities and formation of enzyme-positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30 mg/kg was found to be more effective in reducing the severity of hepatocarcinogenesis.
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PMID:Different starting times of alpha-tocopherol and gamma-tocotrienol supplementation and tumor marker enzyme activities in the rat chemically induced with cancer. 914 29

Hepatocarcinogenesis (HC) induced by various carcinogens such as 1,4-dimethylaminoazobenzene (DAB) is a multistep and complex process. The anticancer efficacy of beta-carotene (beta C) was evaluated by estimating some biochemical parameters during the initiation stage of HC. beta C dietary supplementation partially prevented the rise in delta-aminolevulinate synthetase activity. P 450 levels were dramatically enhanced in all groups studied. beta C administration did not overcome catalase inactivation due to DAB treatment; however, superoxide dismutase activity levels showed to be less decreased in the DAB + beta C animals in comparison to the DAB group. The great enhancement provoked by DAB of glutathione S-transferase, a proposed marker of HC, was partially reversed by beta C. In conclusion, heme pathway regulation, drug metabolism, and natural oxidative defence systems, strikingly modified in DAB fed animals, were partially controlled by provitamin A. The potential use of beta C in preventing carcinogenesis is suggested.
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PMID:beta-Carotene partially prevents the damage induced by 1,4-dimethylaminoazobenzene in mice. 980 23

Hepatocarcinogenesis initiated with N-nitrosodiethylamine (DEN) and that initiated by feeding of a choline-deficient, L-amino acid-defined (CDAA) diet were compared in transgenic male Wistar rats harboring a rat glutathione S-transferase placental form (GST-P) gene (GST-P-Tg rats) and non-transgenic (N-Tg) rats. Eight-week-old GST-P-Tg and N-Tg rats were administered DEN intraperitoneally at 100 mg/kg body weight, subjected to a selection procedure with 2-acetylaminofluorene and CCl4, and killed at the end of weeks 5 and 12. Other groups were fed the CDAA diet for 12 weeks and killed. Five weeks after the DEN treatment, numbers and sizes of gamma-glutamyltransferase (GGT)- or GST-P-positive lesions and 8-hydroxyguanine (8-OHG) levels in the livers were significantly less in GST-P-Tg rats than in N-Tg rats. The lesion numbers were unchanged between the ends of weeks 5 and 12 in GST-P-Tg rats, but decreased in N-Tg rats. The lesion sizes were increased in GST-P-Tg rats, but unchanged in N-Tg rats. While the proliferating cell nuclear antigen labeling indices (PCNA L.I.) in and surrounding the lesions were decreased, more prominently in GST-P-Tg rats than in N-Tg rats, the 8-OHG levels were also decreased but similarly in both cases. After 12 weeks on the CDAA diet, the lesion incidences, numbers and sizes, 8-OHG levels, PCNA L.I. in and surrounding the lesions, and liver injury were significantly less in GST-P-Tg rats than in N-Tg rats. These results indicate that insertion of a rat GST-P transgene alters the early phase of exogenous and endogenous rat hepatocarcinogenesis, presumably due to enhanced detoxification by GST-P expressed both transiently during the initiation and chronically in the altered hepatocyte populations.
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PMID:Inhibition of early-phase exogenous and endogenous liver carcinogenesis in transgenic rats harboring a rat glutathione S-transferase placental form gene. 991 80

This study was designed to determine the effects of dietary n-3/n-6 fatty acid ratios on preneoplastic foci and the microsomal monooxygenase system in rat hepatocarcinogenesis. Male Sprague-Dawley rats were fed four kinds of diets containing 15% (wt/wt) fat with different n-6/n-3 ratios: low ratio (> or = 1.0) with tuna oil, low ratio (> or = 1.0) with perilla oil, moderate ratio (< or = 4.0), and high ratio (< or = 10.0). Hepatocarcinogenesis was induced by diethylnitrosamine and partial hepatectomy. The moderate ratio diet decreased significantly the area and number of placental glutathione S-transferase-positive foci compared with the high ratio diet and low ratio diet with perilla oil. The fatty acid composition of microsomal membrane varied extensively, reflecting the dietary n-6/n-3 ratios. Liver microsomal lipid peroxidation was significantly decreased in the group fed the low ratio diet with tuna oil compared with the moderate and high ratio groups. Glucose-6-phosphatase activity, which reflects membrane stability, was significantly higher in the low ratio groups than in the high ratio group. The monooxygenase activities were increased significantly in the moderate ratio group compared with the high ratio group. These results suggest that a moderate n-6/n-3 ratio (< or = 4.0) may be the most effective in decreasing preneoplastic foci by elevating the monooxygenase activities and n-3 fatty acids in fish oil may have a protective effect by lowering the lipid peroxidation and stabilizing the microsomal membrane during rat hepatocarcinogenesis.
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PMID:Modulation of liver microsomal monooxygenase system by dietary n-6/n-3 ratios in rat hepatocarcinogenesis. 1096 21

This study was conducted to examine the effects of dietary grape extracts on preneoplastic foci formation in rat hepatocarcinogenesis, and related hepatic enzymes. Male Sprague-Dawley rats were fed basal diet or grape diet containing 15% concentrated grape extracts (68 bricks). The grape diet groups were divided into whole-period grape diet group (DEN-GW; grape diet group fed throughout experimental period) and postinitiation grape diet group (DEN-GP; grape diet group fed from post initiation stage) according to the starting time point of the grape diet. Hepatocarcinogenesis was induced by diethylnitrosamine (DEN; 200 mg/kg bw) and 2/3 partial hepatectomy (DEN-B; DEN-treated basal diet group, DEN-GW, and DEN-GP groups), while the control group treated with saline and sham operation (Control group). The formation of placental glutathione (GSH) S-transferase positive (GST-P+) foci in DEN-GW group was moderately but significantly suppressed, however, not in DEN- GP group. Thiobarbituric acid reactive substances content of DEN-GW group was significantly lower than that of DEN-B group. The activity of fatty acid synthase (FAS) in the grape diet groups was decreased about 1/2 of the DEN-B group. The content of GSH and GSH peroxidase activity were increased by carcinogen treatment, but not modulated by grape diet. The activities of GSH S-transferase, p-nitrophenol hydroxylase, and catalase were not affected by diet or treatment. Conclusively, the grape diet-induced reduction of FAS activity that was expressed highly in neoplastic tissues, might be one of the contributing mechanisms of hepatic cancer prevention.
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PMID:Grape extracts suppress the formation of preneoplastic foci and activity of fatty acid synthase in rat liver. 1464 90

The present study was aimed to investigate the chemopreventive effects of Solanum trilobatum (ST) extract against diethylnitrosamine (DEN)-induced hepatocarcinogenesis promoted by Phenobarbital (PB) in Wistar rats. Hepatocarcinogenesis was initiated by a single intraperitoneal injection of DEN (200 mg/kg b.w.) and promoted with PB (0.05%) in basal diet. The experimental study extended for periods of 13 and 26 weeks. Alcoholic extract of ST was orally administered for the entire experimental period after initiation along with commencement of promotion. The chemopreventive effect of ST was assessed from the incidence of nodules, drug metabolizing phase I components such as contents of cytochrome P450, cytochrome b(5), activities of NADPH cytochrome c reductase, NADH - cytochrome b(5) reductase and phase II components such as levels of glutathione, activities of UDP-glucuronyl transferase, glutathione S-transferase and gamma-glutamyl transpeptidase in the liver. Lipid peroxidation at basal and prooxidants-induced (NADPH + ADP + Fe and Ascorbate + Fe) states was assessed in the microsomes. Animals administered with ST extract evidenced significant inhibition of tumor nodular incidence in DEN + PB + ST animals compared to DEN + PB animals, with favorable alterations in the hepatic drug-metabolizing phase I and phase II components. Administration of ST inhibited basal and pro-oxidant-induced lipid peroxidation. The present result suggests the probable mediation of chemoprevention by ST against DEN-induced carcinogenesis by the modulation of drug metabolizing components in the liver of treated animals.
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PMID:Effect of Solanum trilobatum on hepatic drug metabolising enzymes during diethylnitrosamine-induced hepatocarcinogenesis promoted by Phenobarbital in rat. 1730 Jun 97